This is a renewal application for the UCLA Autism Center of Excellence. The primary focus of the UCLA ACE renewal is to understand the relationship between aberrant brain development and core deficits in autism by identifying mechanisms relating genes to brain structure/function and brain to behavior, and to develop effective interventions based on basic experimental and clinical research findings that will change outcomes in autism. In five interdependent projects and cores, our center builds on our expertise in autism genetics, multimodal brain imaging, early detection and analysis of core autism features, and experience in implementing randomized control trials of novel interventions that target these core symptoms. In this renewal application, projects focus on defining longitudinal trajectories of brain and behavioral development in infants with multiple risks for autism (Proj I); infants and toddlers with early signs of autism (Project II), nonverbal school age children with autism (Proj III), and higher functioning children/ adolescents (Project IV), using a shared set of imaging, neurophysiological and neurobehavioral biomarkers, as well as genetic risk and expression analysis (Proj V) in longitudinal studies. This center is focused on understanding both early and later trajectories of emerging and developing functional connectivity and behavioral change in relation to variation in autism phenotypes, defining how genetic risks mediate both imaging and behavioral phenotypes, and altering trajectories through two separate treatments focused on core deficits in ASD, one targeted developing joint attention and social orientation in infants, and one focused on improving language nonverbal children with augmentative pharmacological intervention. Four cores support the scientific goals: an Administrative Core, facilitating scientific progress and providing data management/statistics support; a Diagnostic and Phenotyping Core; a Neuroimaging/Neurophysiology core, and a Research Education and Outreach core. The UCLA ACE benefits from our years of working together as a team. We present a highly integrated center with multiple collaborations across levels of analysis to further a strongly translational research strategy aimed at changing outcomes in children with autism spectrum disorders. RELEVANCE: This is a renewal application for the UCLA Autism Center of Excellence. The UCLA Autism Center of Excellence is dedicated to identifying the causes of autism, discovering how risk factors translate into abnormal brain development, developing and validating novel interventions, and targeting the core deficits to change trajectories and outcomes in individuals with autism spectrum disorder.